Blog

Clinical Trial of Sonodynamic Therapy for Glioblastoma Begins in Milan

Published:
Key Points Sonodynamic therapy (SDT) uses focused ultrasound to activate agents that selectively accumulate in tumor cells and cause cell death.In this trial, researchers will use SDT in patients with newly diagnosed glioblastomas, a primary malignant brain tumor.  The Foundation is funding this important clinical trial.  A clinical trial investigating the safety and feasibility of using sonodynamic therapy (SDT) in patients with newly diagnosed glioblastomas (GBMs), a primary malignant brain tumor, has begun enrolling patients at the Fondazione IRCCS Istituto Neurologico Carlo Besta in Milan, Italy. SDT is an emerging modality for cancer treatment that employs focused ultrasound to interact with an agent to cause cell death only within the tumor. In this pilot trial, researchers will use Insightec’s low-frequency Exablate Neuro focused ultrasound device to activate 5-aminolevulinic acid (5-ALA), an optical imaging agent that accumulates selectively in tumor cells and is commonly used to visualize tumors during surgery. The study is led by Francesco Prada, MD, neurosurgeon and director of the Acoustic Neuroimaging and Therapy Laboratory at Carlo Besto Neurological Institute. Dr. Prada is also a former Focused Ultrasound Foundation fellow and serves as an advisor to the Foundation’s Brain Program. The Foundation is funding this clinical trial.  “The study will assess the safety and feasibility as well as the antitumor effects of SDT on patients with newly diagnosed GBMs,” says Dr. Prada. “The low intensity focused ultrasound interacts with 5-ALA to generate cytotoxic compounds and enhance the immune system, thus destroying tumor cells. SDT offers significant advantages and safety because 5-ALA primarily accumulates in tumor cells, while ultrasound energy can be tightly focused and delivered through the intact skull to the targeted area. FUS and 5-ALA separately are not able to create a damage, it is their interaction at the tumor target that is able to induce tumor damage.” In total, up to 10 patients will receive 5-ALA orally four to six hours before undergoing the focused ultrasound procedure. Then, follow-up scans will be completed at regular intervals to evaluate changes in tumor size. Patients will undergo surgery to remove the tumor approximately two weeks after focused ultrasound, with subsequent chemo- and radiotherapy, which is the traditional treatment method. Patients will then complete a prescribed follow-up of up to three months. “GBMs are the most common and aggressive primary brain tumors,” explains Dr. Prada. “Patients typically only survive an average of 16 months, even with the best care. We must develop better techniques to battle these tumors, and that is one reason we are targeting GBMs in this initial study. However, if we achieve positive results and the data indicate that SDT is safe, we are hopeful that could pave the way for using SDT in other forms of brain tumors with other sensitizers.” Similar SDT studies in patients with recurrent GBM are ongoing in the US at the Ivy Brain Tumor Center at Barrow Neurological Institute and St. Joseph’s Hospital and Medical Center in Phoenix, Arizona, and at MD Anderson Cancer Center in Houston, Texas. To learn more about the Italian clinical trial, please visit clinicaltrials.gov. Another Clinical Trial for Patients with GBMDr. Prada and his colleagues are also addressing patients with GBM in a separate trial using a different mechanism of focused ultrasound to open the BBB to deliver chemotherapy. Learn more about that study.
Read More ...

Review Article: Immunotherapy Delivery for Alzheimer’s Disease

Published:
Key Points This article provides a preclinical and clinical overview of using low-intensity ultrasound plus microbubbles to disrupt the blood-brain barrier for the delivery of immunotherapies in Alzheimer’s disease.It then compares in vitro and in vivo models, strategies for combining therapeutic agents with microbubbles, and techniques to understand observable bioeffects.The authors discuss questions on how in vitro studies can be translated to animal and human applications. Opportunities and Challenges in Delivering Biologics for Alzheimer’s Disease by Low-Intensity Ultrasound Source: Queensland Brain Institute In this review article, Jürgen Götz, PhD, and his team at Queensland Brain Institute first provide an overview of preclinical and clinical trials that have used low-intensity ultrasound plus microbubbles to disrupt the blood-brain barrier (BBB) for the delivery of immunotherapies in Alzheimer’s disease. The immunotherapies described are those that target either amyloid-beta peptides or tau proteins. The article then compares various models for in vitro BBB studies, strategies for combining therapeutic agents with microbubbles, and the impact of super-resolution microscopy on the field. In vitro BBB models may be cellular, two-dimensional, or three-dimensional, and there are many molecular imaging techniques that can be used to understand the bioeffects that occur during these types of experiments. To conclude, the group discusses several treatment development and optimization questions on how in vitro studies can be translated to animal and human applications. See Advanced Drug Delivery Reviews >
Read More ...

Sunnybrook Scientist Publishes Promising Alzheimer’s Study, Elected to Canadian Academy of Health Sciences

Published:
Key Points A research team led by Isabelle Aubert, PhD, published a study showing that focused ultrasound increased delivery of a growth factor and improved cognition in a preclinical model of Alzheimer’s disease.The Canadian Academy of Health Sciences also recently elected Dr. Aubert to its group of 2022 Fellows.Dr. Aubert is a senior scientist at Sunnybrook Research Institute in Toronto. Isabelle Aubert, PhD, and her research team at Sunnybrook Research Institute in Toronto recently completed a study showing that focused ultrasound increased delivery of a growth factor and improved cognition in a preclinical model of Alzheimer’s disease. The study, “Ultrasound Delivery of a TrkA Agonist Confers Neuroprotection to Alzheimer-Associated Pathologies,” was published in the journal Brain. Results from the Alzheimer’s study were captured in a story from Sunnybrook titled “Behind the Research: New Study Finds Focused Ultrasound Enhances Delivery of Brain Therapeutic and Improves Cognition in Alzheimer’s.” In the behind the research article, Dr. Aubert and postdoctoral researcher, Kristiana Xhima, PhD, describe the motivation, results, and interpretation of their work, which will lead to further studies on the affected molecular pathways in the brain. A Brain podcast has also been created to explain and summarize the study. “Our results went beyond what was expected with target engagement on cholinergic neurons alone,” said Dr. Aubert. The researchers caution that although it is promising, the preclinical findings are still at an early stage and not yet ready for translation to clinical trials. This study coincided with Dr. Aubert’s election as a Fellow of the Canadian Academy of Health Sciences (CAHS) for her leadership, distinctive competencies, scientific achievements, and her commitment to advance health science. CAHS recognition is given to health and biomedical scientists and scholars who positively impact the urgent health concerns of Canadians. The 71 recently elected Fellows represent researchers across a wide range of disciplines who “evaluate Canada’s most complex health challenges and recommend strategic, actionable solutions.” “I am honored by this recognition and delighted at the opportunity to serve as scientist, volunteer, and advocate for the global advancement of academic health sciences with CAHS Fellows,” said Dr. Aubert. “I feel very grateful toward my mentors, colleagues, trainees, friends, and family who inspired, contributed, and supported my scientific journey.” Read the Article in Brain > See the Sunnybrook “Behind the Research” Alzheimer’s Story > See Sunnybrook’s Canadian Academy Announcement > Listen to the Brain Podcast >
Read More ...

Yutong Guo, PhD, Named 2022 Andrew J. Lockhart Postdoctoral Fellow

Published:
Key Points Dr. Yutong Guo completed her PhD at the Georgia Institute of Technology and will begin her postdoctoral fellowship at Stanford University.She plans to study how focused ultrasound can be combined with CAR T cell therapy to treat aggressive brain tumors, such as glioblastoma.The one-year fellowship was established in January 2021 by the Lockhart family in honor of their son. Yutong Guo, PhD, has been awarded the 2022 Andrew J. Lockhart Postdoctoral Fellowship in Focused Ultrasound and Immuno-Oncology. The one-year fellowship is designed for early-career researchers as a way for the Foundation to cultivate the next generation of investigators who could advance the development and clinical adoption of focused ultrasound in immuno-oncology. Dr. Guo recently completed her PhD at the Georgia Institute of Technology under the mentorship of Costas Arvanitis, PhD, in the Ultrasound Biophysics and Bioengineering Laboratory. There, her research involved using low-intensity microbubble-enhanced focused ultrasound (MB-FUS) plus nanoparticles to improve the delivery of small interfering RNA in brain tumors. Her studies indicated that the therapy led to a 15-fold higher tumor cell death compared with nanoparticles delivered without MB-FUS. This work was recognized at our recent 8th International Symposium on Focused Ultrasound with a Young Investigator Award. This January, Dr. Guo will join Dr. Katherine Ferrara’s laboratory at Stanford University, where she plans to expand her research to study how low-intensity MB-FUS can be combined with CAR T cell therapy to treat aggressive brain tumors, such as glioblastoma. “I am extremely honored and grateful to have been selected to receive the Lockhart fellowship, which will support me to launch my independent academic career and conduct impactful research on the emerging field of ultrasound cancer immunotherapy,” said Dr. Guo. The Lockhart family established the fellowship in January 2021 in honor of their son, Andrew J. Lockhart, who passed away at the age of 39 from cholangiocarcinoma, a particularly virulent cancer affecting the biliary system of the liver and gallbladder. The Lockhart family are also longtime supporters of the Focused Ultrasound Foundation. Andrew’s parents, Terry and Gene, said, “We believe it will take collaboration and revolutionary ideas to find effective immunotherapies for hard-to-treat cancers like the one that claimed our son Andrew. Our goal is to encourage a new generation of focused ultrasound researchers, and we are pleased to have Dr. Guo as the latest recipient of this fellowship.” “Dr. Guo has demonstrated a clear commitment to advancing the development of unique focused ultrasound and immunotherapy combination approaches,” said Jessica Foley, PhD, the Foundation’s chief scientific officer. “This work could ultimately provide new treatments for hard-to-treat cancers, such as glioblastoma, where patients currently lack effective treatment options. We are excited to see what she accomplishes.”
Read More ...

Call for Manuscripts: Special Collection on Histotripsy

Published:
Key Points The International Journal of Hyperthermia is seeking manuscripts for an upcoming special collection on histotripsy.Suzanne LeBlang, MD, the Foundation’s director of clinical relationships, is one of the guest advisors for the collection.The deadline to submit a manuscript is March 10, 2023. The International Journal of Hyperthermia is requesting manuscripts for an upcoming special collection, “The Art of Histotripsy: A Focused Ultrasound Application that has the Potential to Treat from Head to Toe!” Histotripsy is a non-thermal method of using focused ultrasound to mechanically destroy target tissue. The goal of the collection is to solicit the contribution and submission of articles that describe the current state of the field with respect to understanding the following: Describe the technical aspects of histotripsyProvide a technical description of the mechanisms of action of histotripsy and its subtypes (boiling and nonboiling)Describe approaches to provide imaging guidance for histotripsy treatmentsDetail technical considerations on bypassing the skullDescribe preclinical histotripsy ablation research for varied clinical applicationsDescribe preclinical studies researching the immune response with histotripsyPresent early clinical data with liver ablation and optimal clinical trial designPresent current veterinary applications with histotripsy Suzanne LeBlang, MD, the Foundation’s director of clinical relationships, and Timothy J. Ziemlewicz, MD, associate professor of radiology at the University of Wisconsin, are serving as guest advisors for the collection. “Histotripsy is a rapidly developing area of focused ultrasound with the potential to impact many challenging diseases,” said Dr. Leblang. “At this stage, it is imperative that the field promotes early research and supports a collaborative environment for researchers in this space. We hope this special collection will both increase awareness of this modality and also encourage further studies.” To submit a manuscript, please visit the special collection page on the International Journal of Hyperthermia website. For any pre-submission enquiries, please contact Dr. LeBlang or Dr. Ziemlewicz. The submission deadline is March 10, 2023. Learn More about the Collection >
Read More ...
Cleveland Clinic’s Comprehensive Review of Focused Ultrasound Brain Treatments Meeting Report: European Association of Neuro-Oncology (EANO) 2022 Why It Takes So Long to Develop a Medical Technology (Part 4) Standardization of Focused Ultrasound–Induced Blood-Brain Barrier (BBB) Opening: A Systematic Review of Protocols, Efficacy, and Safety Outcomes Best Practices for Patent Portfolio Impact – How to Patent